title: Selaginella tamariscina (Beauv.) possesses antimetastatic effects on human osteosarcoma cells by decreasing MMP-2 and MMP-9 secretions via p38 and Akt signaling pathways.
abstract: Selaginella tamariscina is a traditional medicinal plant for treatment of some advanced cancers in the Orient. However, the effect of S. tamariscina on metastasis of osteosarcoma and the underlying mechanism remain unclear. We tested the hypothesis that S. tamariscina suppresses cellular motility, invasion and migration and also investigated its signaling pathways. This study demonstrates that S. tamariscina, at a range of concentrations (from 0 to 50 μg/mL), concentration-dependently inhibited the migration/invasion capacities of three osteosarcoma cell lines without cytotoxic effects. Zymographic and western blot analyses revealed that S. tamariscina inhibited the matrix metalloproteinase (MMP)-2 and MMP-9 enzyme activity, as well as protein expression. Western blot analysis also showed that S. tamariscina inhibits phosphorylation of p38 and Akt. Furthermore, SB203580 (p38 inhibitor) and LY294002 (PI3K inhibitor) showed the similar effects as S. tamariscina in U2OS cells. In conclusion, S. tamariscina possesses an antimetastatic activity in osteosarcoma cells by down-regulating MMP-2 and MMP-9 secretions and increasing TIMP-1 and TIMP-2 expressions through p38 and Akt-dependent pathways. S. tamariscina may be a powerful candidate to develop a preventive agent for osteosarcoma metastasis.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Jia-Sin
authors.initials: JS
authors.lastname: Yang
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Hsin-Lin
authors.initials: HL
authors.lastname: Cheng
authors.forename: Ko-Huang
authors.initials: KH
authors.lastname: Lue
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Ko-Hsiu
authors.initials: KH
authors.lastname: Lu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D020834:Ethnopharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D008518:Medicine, East Asian Traditional; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D032503:Selaginellaceae / Q000737:chemistry*; D013624:Taiwan; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000819:agonists / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000819:agonists / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; D010936:Plant Extracts; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: ECM; ERK; JNK; MAPK; MMP; MMP-2; MMP-9; Metastasis; Osteosarcoma; PI3K; Selaginella tamariscina; TIMP; c-Jun N-terminal kinase; extracellular matrix; extracellular signal-regulated protein kinase; matrix metalloproteinase; mitogen-activated protein kinase; phosphatidylinositol 3-kinase; tissue inhibitor of metalloproteinase